Procainamide (original) (raw)
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Summary
Procainamide is a medication used to treat life threatening ventricular arrhythmias.
Generic Name
Procainamide
DrugBank Accession Number
DB01035
Background
A derivative of procaine with less CNS action.
Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 235.3253
Monoisotopic: 235.168462309
Chemical Formula
C13H21N3O
Synonyms
- p-Amino-N-(2-diethylaminoethyl)benzamide
- p-Aminobenzoic diethylaminoethylamide
- Procainamida
- Procainamide
- Procaïnamide
- Procainamidum
- NSC-27461
Indication
For the treatment of life-threatening ventricular arrhythmias.
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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics
Procainamide is an agent indicated for production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Procainamide appears to be similar to that of procaine and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected.
Mechanism of action
Procainamide is sodium channel blocker. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.
Target | Actions | Organism |
---|---|---|
APotassium voltage-gated channel subfamily H member 2 | inhibitor | Humans |
ASodium channel protein type 5 subunit alpha | inhibitor | Humans |
UDNA (cytosine-5)-methyltransferase 1 | other | Humans |
Absorption
75 to 95%
Volume of distribution
- 2 L/kg
Protein binding
15 to 20%
Metabolism
Hepatic
Hover over products below to view reaction partners
Route of elimination
Trace amounts may be excreted in the urine as free and conjugated p-aminobenzoic acid, 30 to 60 percent as unchanged PA, and 6 to 52 percent as the NAPA derivative.
Half-life
~2.5-4.5 hours
Clearance
Not Available
Adverse Effects
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Toxicity
LD50=95 mg/kg (rat, IV); LD50=312 mg/kg (mouse, oral); LD50=103 mg/kg (mouse, IV); LD50=250 mg/kg (rabbit, IV)
Pathways
Pathway | Category |
---|---|
Procainamide (Antiarrhythmic) Action Pathway | Drug action |
Not Available
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug | Interaction |
---|---|
Integrate drug-drug interactions in your software | |
Abacavir | Abacavir may decrease the excretion rate of Procainamide which could result in a higher serum level. |
Abatacept | The metabolism of Procainamide can be increased when combined with Abatacept. |
Abemaciclib | The excretion of Procainamide can be decreased when combined with Abemaciclib. |
Abiraterone | The metabolism of Procainamide can be decreased when combined with Abiraterone. |
Acebutolol | Procainamide may increase the arrhythmogenic activities of Acebutolol. |
Food Interactions
- Avoid alcohol.
- Take with food. Food reduces irritation.
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Ingredient | UNII | CAS | InChI Key |
---|---|---|---|
Procainamide hydrochloride | SI4064O0LX | 614-39-1 | ABTXGJFUQRCPNH-UHFFFAOYSA-N |
International/Other Brands
Biocoryl / Procan / Procapan
Brand Name Prescription Products
Generic Prescription Products
ATC Codes
- C01BA — Antiarrhythmics, class Ia
- C01B — ANTIARRHYTHMICS, CLASS I AND III
- C01 — CARDIAC THERAPY
- C — CARDIOVASCULAR SYSTEM
Drug Categories
- Acids, Carbocyclic
- Agents Causing Muscle Toxicity
- Agents that produce neuromuscular block (indirect)
- Amides
- Aminobenzoates
- Antiarrhythmic agents
- Antiarrhythmics, Class I
- Antiarrhythmics, Class Ia
- Benzamides and benzamide derivatives
- Benzene Derivatives
- Benzoates
- Cardiac Therapy
- Cardiovascular Agents
- Cholinesterase Inhibitors
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index
- Highest Risk QTc-Prolonging Agents
- MATE 1 Substrates
- MATE 1 Substrates with a Narrow Therapeutic Index
- MATE 2 Substrates
- MATE 2 Substrates with a Narrow Therapeutic Index
- MATE substrates
- Membrane Transport Modulators
- Narrow Therapeutic Index Drugs
- Negative Inotrope
- OCT1 inhibitors
- OCT2 Inhibitors
- OCT2 Substrates with a Narrow Therapeutic Index
- para-Aminobenzoates
- QTc Prolonging Agents
- Sodium Channel Blockers
- Voltage-Gated Sodium Channel Blockers
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminobenzamides. These are organic compounds containing a benzamide moiety with an amine group attached to the benzene ring.
Kingdom
Super Class
Class
Benzene and substituted derivatives
Sub Class
Direct Parent
Alternative Parents
Benzamides / Benzoyl derivatives / Aniline and substituted anilines / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives / Primary amines / Organopnictogen compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives show 1 more
Substituents
Amine / Amino acid or derivatives / Aminobenzamide / Aniline or substituted anilines / Aromatic homomonocyclic compound / Benzamide / Benzoyl / Carboxamide group / Carboxylic acid derivative / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Primary amine / Secondary carboxylic acid amide / Tertiary aliphatic amine / Tertiary amine show 10 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
benzamides (CHEBI:8428)
Affected organisms
- Humans and other mammals
UNII
CAS number
51-06-9
InChI Key
REQCZEXYDRLIBE-UHFFFAOYSA-N
InChI
InChI=1S/C13H21N3O/c1-3-16(4-2)10-9-15-13(17)11-5-7-12(14)8-6-11/h5-8H,3-4,9-10,14H2,1-2H3,(H,15,17)
IUPAC Name
4-amino-N-[2-(diethylamino)ethyl]benzamide
SMILES
CCN(CC)CCNC(=O)C1=CC=C(N)C=C1
Synthesis Reference
Victor Chu, Zhu Teng, Steve Goss, Ronald Edwards, Kelle Garvey, Timothy Gorzynski, William Bedzyk, "Synthesis and application of procainamide analogs for use in an immunoassay." U.S. Patent US20050227288, issued October 13, 2005.
General References
Not Available
External Links
Human Metabolome Database
KEGG Compound
PubChem Compound
PubChem Substance
ChemSpider
BindingDB
RxNav
ChEBI
ChEMBL
ZINC
Therapeutic Targets Database
PharmGKB
RxList
Drugs.com
Wikipedia
MSDS
Clinical Trials
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Manufacturers
Not Available
Packagers
- E.R. Squibb and Sons LLC
- Hospira Inc.
- Ivax Pharmaceuticals
- Kaiser Foundation Hospital
- Major Pharmaceuticals
- Mckesson Corp.
- Monarch Pharmacy
- Murfreesboro Pharmaceutical Nursing Supply
- Neuman Distributors Inc.
- PD-Rx Pharmaceuticals Inc.
- Physicians Total Care Inc.
- United Research Laboratories Inc.
Dosage Forms
Form | Route | Strength |
---|---|---|
Capsule | Oral | 375 g |
Injection, solution | Intravenous | |
Capsule | Oral | 250 mg/1 |
Capsule | Oral | 375 mg/1 |
Capsule | Oral | 500 mg/1 |
Injection | Intramuscular; Intravenous | 100 mg/1mL |
Injection | Intramuscular; Intravenous | 1000 mg/1 |
Injection | Intramuscular; Intravenous | 500 mg/1mL |
Injection, solution | Intramuscular; Intravenous | 100 mg/1mL |
Injection, solution | Intramuscular; Intravenous | 500 mg/1mL |
Solution | Intramuscular; Intravenous | 100 mg / mL |
Capsule | Oral | |
Tablet, extended release | Oral | 250 mg |
Tablet, extended release | Oral | 500 mg |
Tablet, extended release | Oral | 750 mg |
Tablet, film coated, extended release | Oral | 1000 mg/1 |
Tablet, film coated, extended release | Oral | 500 mg/1 |
Capsule, gelatin coated | Oral | 250 mg/1 |
Capsule, gelatin coated | Oral | 375 mg/1 |
Capsule, gelatin coated | Oral | 500 mg/1 |
Tablet, film coated | Oral | 250 mg/1 |
Tablet, film coated | Oral | 375 mg/1 |
Tablet, film coated | Oral | 500 mg/1 |
Capsule | Oral | 375 mg |
Capsule | Oral | 500 mg |
Liquid | Intramuscular; Intravenous | 100 mg / mL |
Capsule | Oral | 250 mg |
Prices
Unit description | Cost | Unit |
---|---|---|
Procainamide 500 mg/ml vial | 6.45USD | ml |
Procainamide 100 mg/ml vial | 1.29USD | ml |
Procan Sr 750 mg Sustained-Release Tablet | 0.91USD | tablet |
Procan Sr 500 mg Sustained-Release Tablet | 0.56USD | tablet |
Procan Sr 250 mg Sustained-Release Tablet | 0.4USD | tablet |
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent Number | Pediatric Extension | Approved | Expires (estimated) | Region |
---|---|---|---|---|
US5656296 | No | 1997-08-12 | 2014-08-12 |
State
Solid
Experimental Properties
Property | Value | Source |
---|---|---|
melting point (°C) | 165-169 °C | Not Available |
water solubility | 5050 mg/L | Not Available |
logP | 0.88 | HANSCH,C ET AL. (1995) |
pKa | 9.32 | SANGSTER (1994) |
Predicted Properties
Property | Value | Source |
---|---|---|
Water Solubility | 3.02 mg/mL | ALOGPS |
logP | 1.42 | ALOGPS |
logP | 0.95 | Chemaxon |
logS | -1.9 | ALOGPS |
pKa (Strongest Acidic) | 15.75 | Chemaxon |
pKa (Strongest Basic) | 9.04 | Chemaxon |
Physiological Charge | 1 | Chemaxon |
Hydrogen Acceptor Count | 3 | Chemaxon |
Hydrogen Donor Count | 2 | Chemaxon |
Polar Surface Area | 58.36 Å2 | Chemaxon |
Rotatable Bond Count | 6 | Chemaxon |
Refractivity | 72.25 m3·mol-1 | Chemaxon |
Polarizability | 27.69 Å3 | Chemaxon |
Number of Rings | 1 | Chemaxon |
Bioavailability | 1 | Chemaxon |
Rule of Five | Yes | Chemaxon |
Ghose Filter | Yes | Chemaxon |
Veber's Rule | No | Chemaxon |
MDDR-like Rule | No | Chemaxon |
Predicted ADMET Features
Property | Value | Probability |
---|---|---|
Human Intestinal Absorption | + | 0.9561 |
Blood Brain Barrier | + | 0.9675 |
Caco-2 permeable | + | 0.666 |
P-glycoprotein substrate | Substrate | 0.7739 |
P-glycoprotein inhibitor I | Non-inhibitor | 0.9452 |
P-glycoprotein inhibitor II | Non-inhibitor | 0.9654 |
Renal organic cation transporter | Non-inhibitor | 0.7526 |
CYP450 2C9 substrate | Non-substrate | 0.8624 |
CYP450 2D6 substrate | Substrate | 0.8919 |
CYP450 3A4 substrate | Non-substrate | 0.6306 |
CYP450 1A2 substrate | Non-inhibitor | 0.9046 |
CYP450 2C9 inhibitor | Non-inhibitor | 0.9384 |
CYP450 2D6 inhibitor | Non-inhibitor | 0.9231 |
CYP450 2C19 inhibitor | Non-inhibitor | 0.9606 |
CYP450 3A4 inhibitor | Non-inhibitor | 0.9238 |
CYP450 inhibitory promiscuity | Low CYP Inhibitory Promiscuity | 0.8833 |
Ames test | Non AMES toxic | 0.7822 |
Carcinogenicity | Non-carcinogens | 0.5352 |
Biodegradation | Not ready biodegradable | 0.9855 |
Rat acute toxicity | 2.1133 LD50, mol/kg | Not applicable |
hERG inhibition (predictor I) | Weak inhibitor | 0.9454 |
hERG inhibition (predictor II) | Non-inhibitor | 0.648 |
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)
Mass Spec (NIST)
Not Available
Spectra
Chromatographic Properties
Collision Cross Sections (CCS)
Adduct | CCS Value (Å2) | Source type | Source |
---|---|---|---|
[M-H]- | 168.7710142 | predicted | DarkChem Lite v0.1.0 |
[M-H]- | 155.32811 | predicted | DeepCCS 1.0 (2019) |
[M+H]+ | 169.1182142 | predicted | DarkChem Lite v0.1.0 |
[M+H]+ | 157.68611 | predicted | DeepCCS 1.0 (2019) |
[M+Na]+ | 168.9309142 | predicted | DarkChem Lite v0.1.0 |
[M+Na]+ | 163.82333 | predicted | DeepCCS 1.0 (2019) |
Targets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661).
Specific Function
C3HC4-type RING finger domain binding
Gene Name
KCNH2
Uniprot ID
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
- Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). It is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946). This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (PubMed:19074138). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity).
Specific Function
ankyrin binding
Gene Name
SCN5A
Uniprot ID
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
- Weiss R, Barmada MM, Nguyen T, Seibel JS, Cavlovich D, Kornblit CA, Angelilli A, Villanueva F, McNamara DM, London B: Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. Circulation. 2002 Feb 12;105(6):707-13. [Article]
- Brugada R, Brugada J, Antzelevitch C, Kirsch GE, Potenza D, Towbin JA, Brugada P: Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation. 2000 Feb 8;101(5):510-5. [Article]
- Chen SM, Kuo CT, Lin KH, Chiang FT: Brugada syndrome without mutation of the cardiac sodium channel gene in a Taiwanese patient. J Formos Med Assoc. 2000 Nov;99(11):860-2. [Article]
- Brugada J, Brugada R, Brugada P: [Brugada syndrome]. Arch Mal Coeur Vaiss. 1999 Jul;92(7):847-50. [Article]
- Brugada J, Brugada P, Brugada R: The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome. Europace. 1999 Jul;1(3):156-66. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other
General Function
Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306).
Specific Function
DNA (cytosine-5-)-methyltransferase activity
Gene Name
DNMT1
Uniprot ID
Uniprot Name
DNA (cytosine-5)-methyltransferase 1
Molecular Weight
183163.635 Da
References
- Oelke K, Lu Q, Richardson D, Wu A, Deng C, Hanash S, Richardson B: Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum. 2004 Jun;50(6):1850-60. [Article]
- Januchowski R, Jagodzinski PP: Effect of 5-azacytidine and procainamide on CD3-zeta chain expression in Jurkat T cells. Biomed Pharmacother. 2005 Apr;59(3):122-6. [Article]
- Lee BH, Yegnasubramanian S, Lin X, Nelson WG: Procainamide is a specific inhibitor of DNA methyltransferase 1. J Biol Chem. 2005 Dec 9;280(49):40749-56. Epub 2005 Oct 17. [Article]
- Scheinbart LS, Johnson MA, Gross LA, Edelstein SR, Richardson BC: Procainamide inhibits DNA methyltransferase in a human T cell line. J Rheumatol. 1991 Apr;18(4):530-4. [Article]
Enzymes
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
- Lessard E, Hamelin BA, Labbe L, O'Hara G, Belanger PM, Turgeon J: Involvement of CYP2D6 activity in the N-oxidation of procainamide in man. Pharmacogenetics. 1999 Dec;9(6):683-96. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Specific Function
acetylcholinesterase activity
Gene Name
BCHE
Uniprot ID
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
- Bailey DN: Amitriptyline and procainamide inhibition of cocaine and cocaethylene degradation in human serum in vitro. J Anal Toxicol. 1999 Mar-Apr;23(2):99-102. [Article]
- Page JD, Wilson IB, Silman I: Butyrylcholinesterase: inhibition by arsenite, fluoride, and other ligands, cooperativity in binding. Mol Pharmacol. 1985 Apr;27(4):437-43. [Article]
Transporters
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable).
Specific Function
acetylcholine transmembrane transporter activity
Gene Name
SLC22A2
Uniprot ID
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
- Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [Article]
- Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. [Article]
- Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [Article]
- Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. [Article]
- Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS: The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. J Pharmacol Exp Ther. 2002 Dec;303(3):959-68. [Article]
- Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. [Article]
- Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930).
Specific Function
(R)-carnitine transmembrane transporter activity
Gene Name
SLC22A1
Uniprot ID
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
- Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [Article]
- Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. [Article]
- Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [Article]
- Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [Article]
- Green RM, Lo K, Sterritt C, Beier DR: Cloning and functional expression of a mouse liver organic cation transporter. Hepatology. 1999 May;29(5):1556-62. [Article]
- Zhang L, Dresser MJ, Chun JK, Babbitt PC, Giacomini KM: Cloning and functional characterization of a rat renal organic cation transporter isoform (rOCT1A). J Biol Chem. 1997 Jun 27;272(26):16548-54. [Article]
- Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS: The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. J Pharmacol Exp Ther. 2002 Dec;303(3):959-68. [Article]
- Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [Article]
- Grundemann D, Gorboulev V, Gambaryan S, Veyhl M, Koepsell H: Drug excretion mediated by a new prototype of polyspecific transporter. Nature. 1994 Dec 8;372(6506):549-52. [Article]
- Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity).
Specific Function
monoamine transmembrane transporter activity
Gene Name
SLC22A3
Uniprot ID
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
- Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable).
Specific Function
(R)-carnitine transmembrane transporter activity
Gene Name
SLC22A5
Uniprot ID
Uniprot Name
Organic cation/carnitine transporter 2
Molecular Weight
62751.08 Da
References
- Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. [Article]
- Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [Article]
- Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [Article]
- Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:22206629, PubMed:22569296, PubMed:29530864). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (PubMed:15795384, PubMed:29530864, PubMed:33124720). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (PubMed:22206629). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (PubMed:22206629, PubMed:22569296). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:15795384, PubMed:22206629). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (PubMed:35307651).
Specific Function
acetylcholine transmembrane transporter activity
Gene Name
SLC22A4
Uniprot ID
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
- Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [Article]
- Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable).
Specific Function
antiporter activity
Gene Name
SLC47A1
Uniprot ID
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
- Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [Article]
- Motohashi H, Inui K: Organic cation transporter OCTs (SLC22) and MATEs (SLC47) in the human kidney. AAPS J. 2013 Apr;15(2):581-8. doi: 10.1208/s12248-013-9465-7. Epub 2013 Feb 22. [Article]
- Somogyi A, Muirhead M: Pharmacokinetic interactions of cimetidine 1987. Clin Pharmacokinet. 1987 May;12(5):321-66. doi: 10.2165/00003088-198712050-00002. [Article]
- Ito S, Kusuhara H, Yokochi M, Toyoshima J, Inoue K, Yuasa H, Sugiyama Y: Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. J Pharmacol Exp Ther. 2012 Feb;340(2):393-403. doi: 10.1124/jpet.111.184986. Epub 2011 Nov 9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney.
Specific Function
antiporter activity
Gene Name
SLC47A2
Uniprot ID
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
- Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [Article]
- Motohashi H, Inui K: Organic cation transporter OCTs (SLC22) and MATEs (SLC47) in the human kidney. AAPS J. 2013 Apr;15(2):581-8. doi: 10.1208/s12248-013-9465-7. Epub 2013 Feb 22. [Article]
- Somogyi A, Muirhead M: Pharmacokinetic interactions of cimetidine 1987. Clin Pharmacokinet. 1987 May;12(5):321-66. doi: 10.2165/00003088-198712050-00002. [Article]
- Ito S, Kusuhara H, Yokochi M, Toyoshima J, Inoue K, Yuasa H, Sugiyama Y: Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. J Pharmacol Exp Ther. 2012 Feb;340(2):393-403. doi: 10.1124/jpet.111.184986. Epub 2011 Nov 9. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 01, 2024 12:45